The development of manufacturing processes for spray dried inhalation powders involves two challenging constraints: i) a very small particle size is required (with a mean diameter below 5 microns, typically below 3 microns); and ii) the particle size should not be allowed to increase during scale-up (despite the fact that the majority of powders spray dried for oral dosage delivery will tend to increase in particle size during scale-up). These constraints pose important challenges during development, as current off-the-shelf atomization systems lose efficiency when having to manage an increase in throughput upon scale-up. Such loss of efficiency makes necessary the use of a larger quantity of gas for atomization, which leads to distinct challenges depending on the type of atomization system used:                a) In the case of two-fluid external mixture nozzles (high consumers of atomization gas at low pressures), the flow rate of atomization gas may increase to such an extent that the drying chamber size and the rest of the process train may become under-dimensioned for the process (as the atomization gas flow rate requirement can increase, theoretically, to a demand of 30-50% of the total gas flow rate in the spray dryer).        b) For two-fluid internal mixture nozzles (low consumers of atomization gas at high pressures), an increase of atomization gas flow rate may promote such an increase in pressure drop in the nozzle that the pressure of the gas feed lines may often require very complex and expensive upgrades.        
While such challenges might be overcome through engineering upgrades to the spray dryer process train, there remains an even more difficult challenge to address, since there is still the potential for the droplet size to be outside the intended range upon scale-up. It is not uncommon that the nozzle being applied at the smaller scale cannot be directly applied at the larger scale as its operating ranges are exceeded. Additionally, selecting a new nozzle is typically complex, time-consuming and expensive as extensive testing is required. Furthermore, there are no guarantees that such process development activities lead to a successful identification of an adequate candidate nozzle, as there are physical limitations to atomize large flow rates of liquid into small droplets within the target inhalation range. Hence, the current approach to controlling particle size within the inhalation range upon scale-up is limited by nozzle design (external or internal mixture, and nozzle model) and atomization gas flow rate. A different option for controlling particle size would be to decrease solids concentration in the feed mixture, but this is not a recommended approach as it negatively affects the process throughput and cycle time, and ultimately its feasibility from a process economics perspective.
The concept of using multi-nozzle atomization for combining high feed capacity with fine atomization for both pressure nozzles and two-fluid nozzles is known in the art [Green, D; Perry, R. “Perry's chemical engineers' handbook” (2008)]. The spray drying literature includes additional examples where multi-nozzle arrangements were used. For example, US 2002/0007869 discloses a multi-nozzle electrospraying method for the production of nanoparticles with high mass throughput.
WO 03/090893 discloses a process that uses a multi-nozzle apparatus to promote powder agglomeration with negligible product deposits on the walls, through reintroduction of the fines near the main spray plume.
In US 2007/0148325 a granulation method is disclosed for the production of fine aqueous particles using the necessary number of nozzles equivalent to those of conventional design.
A paper by Turton et al. [Turton, R; Cheng, X. “The scale-up of spray coating processes for granular solids and tablets”; Powder Technology 150 (2005) 78-85] discloses a spray coating process for granular solids and tablets that makes use of multiple nozzles to cover a wider area.
U.S. Pat. No. 8,524,279 discloses a process mostly intended for inhalation products that report the use of a multi-nozzle atomizer comprised of a central gas nozzle and a plurality of atomization nozzles around such central gas nozzle. The central gas nozzle is used to minimize spray plume interactions and to control the final powder characteristics, while the feed mixture is atomized in the atomization nozzles.
Whilst such examples mostly disclose multi-nozzle systems targeted for an increase in process throughput, and in some cases enabling the production of particles in the inhalable range, there remains a need in inhalation spray drying for a simple means of controlling particle size upon scale-up. The invention herein disclosed overcomes the shortcomings identified in the prior art, by using multiple low throughput off-the-shelf nozzles. The ratio between liquid and atomization gas flow rate can be maintained as constant in each nozzle across spray dryer scales, which leads to similar sized droplets across scales and eliminates the challenges faced during scale-up that were previously described. This enables a direct scale-up of the process since the operating conditions used in the smaller scale can be directly used in a larger scale spray dryer as each nozzle is geometrically the same across scales. In this way, the single scale-up action to be conducted will be to increase the number of nozzles to be used proportionally to the scale of the spray drying unit. Hence, the idea herein disclosed comprises two innovative concepts that overcome the limitations found in the art and expedites process development:                1) The ability to generate particles in the inhalable range (that is, characterized by a volumetric distribution with a mean geometric size below 5 microns), regardless of the required throughput; the high-throughput multi-nozzle systems that can be currently found in the art do not disclose such critical performance criterion, and        2) Meeting the target particle size range with the use of the same nozzle regardless of the scale (only the number of nozzles is being changed, not the model and type). The multi-nozzle systems that can be currently found available consider different variations/models when throughput is required to be increased above certain ranges.        
Hence, the conventional pharmaceutical spray drying methods used in the production of inhalation powders are limited in terms of fulfillment of critical quality attributes (namely in what concerns the particle size distribution) when higher throughputs are required; the proposed concept is expected to overcome this limitation and, additionally, to expedite process development.